Figure 3:

Mechanisms of enhancing natural Treg (nTreg) and induced Treg (iTreg) for the treatment of nervous system pathologies. Currently, there are three main areas of research dedicated to Treg-enhancing therapies: Stabilization of nTreg survival and function, engineering antigen-specific Treg responses, and utilization of immune-modulatory agents to induce peripheral populations. To stabilize nTreg populations, immunosuppressive markers and transcription factors can be maintained through polarizing cytokines and cell activation, demethylation of the Treg-specific demethylated region (TSDR) using methyltransferases, and CRISPR/Cas9 gene editing to generate stable expression of FoxP3. To engineer antigen specificity, researchers are focusing on antigen-specific T cell receptor (TCR) expression, chimeric antigen receptor (CAR) expression, and transformation of antigen-specific Teff into Treg through lentiviral transduction of FoxP3. To generate iTreg populations, direct administration of Treg-inducing agents such as low-dose IL-2, GM-CSF, bee venom, or CD3 mAb are being utilized. Additionally, ex vivo expansion of dysfunctional Treg using these immune agents followed by autologous adoptive transfer is being explored.